Acetic anhydride acetanilide from

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

Production is by the acetylation of 4-aminophenol. This can be achieved with acetic acid and acetic anhydride at 80°C (191), with acetic acid anhydride in pyridine at 100°C (192), with acetyl chloride and pyridine in toluene at 60°C (193), or by the action of ketene in alcohoHc suspension. 4-Hydroxyacetanihde also may be synthesized directiy from 4-nitrophenol The available reduction—acetylation systems include tin with acetic acid, hydrogenation over Pd—C in acetic anhydride, and hydrogenation over platinum in acetic acid (194,195). Other routes include rearrangement of 4-hydroxyacetophenone hydrazone with sodium nitrite in sulfuric acid and the electrolytic hydroxylation of acetanilide [103-84-4] (196). 

At high temperatures with low catalyst concentration the formation of acetanilides is favored. Maleic anhydride and acetanilides may be formed directly from the mixed anhydride by an initial attack of the nitrogen on the acetate carbonyl, but this process would involve a seven membered ring transition state. Another possible route to the formation of maleic anhydride and the acetanilides is participation by neighboring carbonyl in loosening the amide carbon-nitrogen bond to the extent that the amine can be captured by acetic anhydride as shown in path D. 

At this point aniline can be isolated. You could reduce the solubility of aniline by dissolving in the steam distillate 0.2 g of sodium chloride per milliliter, extract the aniline with 2-3 portions of dichloromethane, dry the extract, distill the dichloromethane (bp 4rC), and then distill the aniline (bp 184°C). Or the aniline can be converted directly to acetanilide. The procedure calls for pure aniline, but note that the first step is to dissolve the aniline in water and hydrochloric acid. Your steam distillate is a mixture of aniline and water, both of which have been distilled. Are they not both water-white and presumably pure Hence, an attractive procedure would be to assume that the steam distillate contains the theoretical amount of aniline and to add to it, in turn, appropriate amounts of hydrochloric acid, acetic anhydride, and sodium acetate, calculated from the quantities given in Experiment 2. 

Experiment Add 1 c.c. of aniline to 1 c.c. of acetic anhydride, heat to incipient ebullition, and then, after cooling, add twice the volume of water. The crystals of acetanilide separate out easily if the walls of the vessel be rubbed with a glass rod these are filtered off, and may be recrystallised from a little hot water. 

The nitration of acetanilide with mixed acid yields nitroacetanilides in which the ortho para ratio is less than 0.1. When the nitration medium is nitric acid, this ratio is 0.7, when acetyl nitrate in acetic anhydride is used, the product is almost entirely o-nitroacetanilide. No satisfactory explanation has been given for these results. The 40-50 per cent yield of m-nitro-aniline that results from the nitration of aniline in mixed acid or in nitric acid can be explained in the following manner. In the strong acids, nitric and sulfuric acid, aniline is largely ionized. 

The freshly redistilled aniline, is almost a colourless oily liquid which being practically insoluble in water. Therefore, before carrying out the acetylation aniline has got to be made soluble in the aqueous medium. It can be accomplished by adding requisite amormt of concentrated HCl whereby the highly reactive amino function easily takes up a proton from the dissociation of HCl in water, get protonated to yield aniline hydrochloride that is water-soluble. Subsequently, the soluble form of aniline is reacted with acetic anhydride in the presence of sodium acetate. The acetate ion obtained from the hydrolysis of the salt (sodium acetate) helps to sustain the acetylation reaction in the forward direction to 3ueld acetanilide completely. 

The synthesis of SFs-substituted phenothiazine was disclosed in a patent from Smith, Kline French Laboratories (63USP3107242). 3-SFs-Acetanilide (120), prepared by acetylation of d-SFs-aniline (39) with acetic anhydride, was first condensed with bromobenzene under basic conditions, in the presence of Cul and copper-bronze powder, and after add hydrolysis provided 3-SFs-diphenylamine (121). This product was then fused with sulfur in the presence of a catalytic amount of iodine to give 2-SFs-phenothiazine (122) in unreported yield (Scheme 34). 

Acetanilide is obtained from aniline and acetic anhydride. It is mainly used in the production of sulfonamide chemotherapeutics those are obtained by the reaction of acetanilide with chlorosulfonic acid, followed by reaction with a primary amine and subsequent deacylation. 

The antipyretic (fever-reducing substance) acetanilide is an amide prepared from aniline and acetic anhydride. 

An aqueous solution of acetic acid containing 0.1>1.0 millimole per gram is prepared from acetic anhydride. Its specific activity of acetic anhydride was determined by treating a portion with an excess of aniline to form acetanilide which was crystallized from water and assayed in dioxane-naphthalene scintillator solution. 

For the determination of acetanilide, to an aliquot part of the filtrate from the iodide precipitation add sodium sulphite and sodium bicarbonate in slight excess add 2 drops of acetic anhydride and extract with three 60-ml portions of chloroform. Evaporate the chloroform to low bulk, add 10 ml of dilute sulphuric acid and evaporate the rest of the chloroform. Add 20 ml of water and digest on a water-bath for one hour. Add 10 ml of concentrated hydrochloric acid and titrate with 0 1 N potassium bromate-bromide, adding the volumetric solution very slowly to the well-shaken mixture until a faint yellow colour remains. Standardise the bromate-bromide solution against pure acetanilide. 

Alkylation of amines has received attention from several groups. Some 2-(l-thiophenoxybutyl)-acetanilides (160) have been obtained by [2,3]-sigmatropic rearrangement of azasulphonium ylides (161), formed from the sulphimine (162) by reaction with acetic anhydride (Scheme 24). 

In the case of ammonia, acetamide is formed the product with aniline is acetanilide, The second substance formed is the aniline salt of acetic acid this is soluble in water and is readily removed when the product of the reaction is crystallized. The preparation of anilides in this way from acid anhydrides is often effected in the identification of anhydrides. The anilides are solids, which can be readily purified as a consequence, an identification can be accomplished with a very small amount of a substance. 

Ethoxy groups have been determined by oxidizing a sample with chromic anhydride and subsequently analysing an aliquot of the reaction solution for acetic acid content [209]. The determination of hydroxyethyl groups in the form of acetanilide obtained quantitatively from the initial sample during pyrolysis at 400°C for 10 min has been described [210]. 

The observation on GA-catalyzed hydrolysis is in contrast to the GB catalysis seen in the buffer-catalyzed hydrolysis of P-lactams of penicillins. " Thus, the probable mechanism of buffer catalysis in this case involves SA-nucleophilic catalysis (Scheme 2.44). The evidence for this catalytic proposal comes from the following observations (1) the mixed acid anhydride intermediate (Intn) has been trapped with aniline to give acetanilide as identified by HPLC (2) the kinetic runs for hydrolysis of A-benzyl-P-snltam in acetate buffers revealed biphasic plots of observed absorbance vs. reaction time an initial exponential bnrst of UV... 

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